Arjen P. TinkeJanssen R&DDepartment of Chemical Technology and Process Control (CTPC)Turnhoutseweg 30B‐2340 Beerse (BELGIUM)

Powder Flow: the missing link in the evolution of powder characterization

Colloids

Suspensions       =          Solids            +           Liquids

Powders           =             Solids            +          Liquids           +         Gasses

A ‘suspension’ is not so much different than a ‘powder’

Is it?...Particle‐particle interaction

• Cohesion• Repulsion• Friction• Interlocking

Product variables that influence behaviour• Size• Shape• Surface texture (roughness)• Surface area

External variables that influence behaviour• Consolidation• Aeration• Flow (shear) Rate• Moisture• Electrostatic Charge• Storage Time• Porosity• Potential for electrostatic charge

• Hygroscopicity• Hardness / Friability• Amorphous content• Density• Cohesion• Adhesion• Elasticity• Plasticity

Powder

Particle Size May Say It AllParticle size may have a large effect on bulk behaviour

• Flowability / Rheology• Sedimentation rate• Abrasiveness• Explosion• Dissolution• etc.

Dissolution rate constant

Noyes‐Whitney equation

Particle size dependency

Laser DiffractionApplication area• QC• R&D

Added value• Golden standard• Black box

Sub Micron Sizing

Particle Size Distribution                               Imaging                                        Bulk Characteristics

Solid State                                               Foreign Material                                  IdentificationCharacteristics

• Laser Diffraction• Dynamic Light Scattering• (Automated) Static Image Analysis• Dynamic Image Analysis

• SEM• Optical Microscopy

• DSC• XRD• Dynamic Vapor Sorption

• Optical Particle Counting• Dynamic Image Analysis

• IR and Raman Microscopy

• Helium Pycnometry• Gas Adsorption

Particle Characterization

Bench Top SEM

d10 (m) d50 (m) d90 (m)

Batch A 1.8 5.7 11.4

Batch B 1.9 5.9 12.3

We’re Missing SomethingA

B

Fluid Imaging

Drug Substance

Chemical Purity

Physical Purity

Powder Characteristics

Quality Aspects

Powders in Pharm Industry

Cohesive

Aeratable

Sand‐like

Spoutable

Milling chamber completely filled with powder

Flow Obstruction

Obstruction of exit holes

Flowability Brittleness Milling

Shear                     Impact Intended BreakageNon‐Intended Breakage

Crystallization

ConditioningPackaging & Transport

• Cohesion• Friction• Interlocking

• Mechanical Properties

• Particle Size Distribution• Up‐ and Down‐Scaling• Modelling• PAT

• Structural Disorder• Relaxation• Surface Energy

• Tribo Electrification(Static Charge)

• Particle Size• Morphology• Product Characteristics (e.g., flowability, mechanical properties)

Solid‐Liquid Separation (incl. Drying) PATMorphology

Powder Technology

Dynamic Image Analysis

Powder Flowability Powder Rheology                                Particle Shape Distribution                      

Surface Energy                                      Surface Charge                                  Mechanical Properties/ Structure

• Bulk‐and‐Tap Density• Static Angle‐of‐Repose • Dynamic AOR

• Inverse GC• TAM

• Faraday cup• Charge decay analysis

• Nano identation• Micro hardness testing

• Powder Rheology

Powder Characterization

• (Automated) Static Image Analysis –Optical Microscopy

Particle ShapeStatic Image Analysis

For rectangular particlesthe laser diffraction (LD)particle size distributionprofile can be calculatedfairly well from the length and the width of the particles.

Powder FlowabilityU.S. Pharmacopoeia<267> Hg porosimetry<429> Laser diffraction<601> Inhalation<616> Bulk and tapped density<699> Helium pycnometry<776> Optical microscopy<786> Sieve testing<811> Powder fineness<846> Specific surface area<1174> Powder flow

Funnel                 Static AOR                       BTD                   Dynamic AOR

Powder Rheology

Batch (*)(g.cm‐3)

[o](g.cm‐3)

[n](g.cm‐3)

n½ H[n] C[n]

Batch C 1.30 0.40 0.45 16.0 1.12 10.3 14.1

Flow Behaviour C HExcellent 10 1.00‐1.11Good 11‐15 1.12‐1.18Fair 16‐20 1.19‐1.25Passable 21‐25 1.26‐1.34Poor 26‐31 1.35‐1.45Very poor 32‐37 1.46‐1.59Very, very poor > 38 > 1.60

Bulk-and-tap density data(*) - measured with helium pycnometry[o] - bulk density (g.cm-3)[n] - tap density (g.cm-3)n½ - compaction kinetic factorH[n] - Hausner ratio (H[n]=[n]/ [o])C[n] - Compressibility factor, or Carr index (H[n]=100/(100-C[n]) - characteristic relaxation time obtained from the fit of the experimental results

Batch Cohesion(kPa)

UYS(kPA)

MPS(kPA)

FF AIF(o)

Measurement Vessel

Batch C 2.82 11.2 20.7 1.85 36.4 25 mm  10 mL

Shear cell test resultsUYS - Unconfined Yield StrengthMPS - Major Principle StressFF - Flow FunctionAIF - Angle of Internal Friction

Type of Flow FFFree‐flowing 10 < FF  Easy‐flowing 4 < FF < 10Cohesive 2 < FF > 4

Very cohesive and non‐flowing

FF < 2

Classification of powder flowability after Jenike

Scale of flowabilityData taken from USP <1174>

FT4 Powder TesterDynamic Flow• BFE ‐ Basic Flowability Energy (mJ)• SE ‐ Specific Energy (mJ/g)• SI ‐ Stability Index• FRI ‐ Flow Rate Index• AE ‐ Aerated Energy (mJ)• AR ‐ Aeration Ratio• CE ‐ Consolidated Energy

Bulk• CBD ‐ Conditioned Bulk Density (g/mL)• CPS ‐ Compressibility Percentage (%)• PD ‐ Pressure Drop across the Powder Bed

Shear• C ‐ Cohesion (kPa)• FF ‐ Flow Function• AIF ‐ Angle of Internal Friction (o)• WF ‐ Wall friction

Process• Flow (Obstruction)• Conveying• Segregation• Attrition• Caking• Electrostatics• Moisture• Agglomeration• etc.

‘Powder Flow’

Fingerprint

Supportive Data

Conclusions• PSD measurements work well in QC, but are not sufficient in R&D

• ‘Powder Flow’ is a broad area, which is more about ‘Flow Obstruction’ than about ‘Flow’

• PHARMACOPOEIA• Relevant for QC• Less for R&D

• HOWCharacterization of ‘Powder Behaviour’

• Flowability testing• Powder rheology• Powder testing (FT4)

• WHYCharacterization of ‘Powder Characteristics’ 

• Image analysis• Static charge• Surface energy• Etc.

Thank you for your attention!